Recent reports have demonstrated that the hypothalamic releasing hormone, thyrotropin releasing factor (pGlu-His-ProNH2), is also present in extrahypothalamic areas in many vertebrates. Furthermore, it has been reported that the administration of the synthetic peptide leads to an alteration in neuronal function in rodents as well as in man. These findings have led to a series of investigations in which the effect of TRF on amine metabolism and on neuronal activity in the vertebrate central nervous system have been studied. The aim of the proposed study is to investigate the mechanism of action of TRF on identified gastropod neurons using intracellular recording techniques combined with iontophoretic application of TRF. The gastropod isolated ganglion preparation has been chosen for the following reasons: 1) Much is known about the connections of snail ganglionic neurons and the nature of chemical transmission occurring at the synapses of identified neurons. 2) Gastropod neurons are large and can be impaled easily with several electrodes under visual guidance. 3) Although there are no axosomatic synapses, functional receptors are present on the soma. Therefore, agonist-receptor interactions can be studied in the absence of presynaptic influences. 4) Recent reports from this laboratory have demonstrated that snail ganglia contain endogenous TRF. The effects of iontophoretically applied TRF, alone or in combination with putative neurotransmitter substances known to alter the membrane permeability in the neurons under study, will be assessed by measuring 1) alterations in the resting membrane potential of silent neurons; 2) alterations of firing frequencies of spontaneously firing neurons; 3) changes in membrane resistance; 4) if effects of TRF can be detected by these means, nature of the response will be further analyzed. These experiments should provide information on mode of action of TRF and may help to elucidate whether TRF acts like a transmitter substance or whether it modulates response of the postsynaptic membrane to neurotransmitter.